-
Expert Review of Clinical Pharmacology Oct 2022Platelets play a key role in arterial thrombosis and antiplatelet therapy is pivotal in the treatment of cardiovascular disease. Current antiplatelet drugs target... (Review)
Review
INTRODUCTION
Platelets play a key role in arterial thrombosis and antiplatelet therapy is pivotal in the treatment of cardiovascular disease. Current antiplatelet drugs target different pathways of platelet activation and show specific pharmacodynamic and pharmacokinetic characteristics, implicating clinically relevant drug-drug interactions.
AREAS COVERED
This article reviews the role of platelets in hemostasis and cardiovascular thrombosis, and discusses the key pharmacodynamics, drug-drug interactions and reversal strategies of clinically used antiplatelet drugs.
EXPERT OPINION
Antiplatelet therapies target distinct pathways of platelet activation: thromboxane A synthesis, adenosine diphosphate-mediated signaling, integrin αβ (GPIIb/IIIa), thrombin-mediated platelet activation via the PAR1 receptor and phosphodiesterases. Key clinical drug-drug interactions of antiplatelet agents involve acetylsalicylic acid - ibuprofen, clopidogrel - omeprazole, and morphine - oral P2Y inhibitors, all of which lead to an attenuated antiplatelet effect. Platelet function and genetic testing and the use of scores (ARC-HBR, PRECISE-DAPT, ESC ischemic risk definition) may contribute to a more tailored antiplatelet therapy. High on-treatment platelet reactivity presents a key problem in the acute management of ST-elevation myocardial infarction (STEMI). A treatment strategy involving early initiation of an intravenous antiplatelet agent may be able to bridge the gap of insufficient platelet inhibition in high ischemic risk patients with STEMI.
Topics: Humans; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Drug Therapy, Combination; Clopidogrel; Thrombosis; Purinergic P2Y Receptor Antagonists
PubMed: 36065676
DOI: 10.1080/17512433.2022.2121702 -
European Journal of Pharmacology Jan 2020Aspirin (acetylsalicylic acid), the oldest synthetic drug, was originally used as an anti-inflammatory medication. Being an irreversible inhibitor of COX... (Review)
Review
Aspirin (acetylsalicylic acid), the oldest synthetic drug, was originally used as an anti-inflammatory medication. Being an irreversible inhibitor of COX (prostaglandin-endoperoxide synthase) enzymes that produce precursors for prostaglandins and thromboxanes, it has gradually found several other applications. Sometimes these applications are unrelated to its original purpose for example its use as an anticoagulant. Applications such as these have opened opportunities for new treatments. In this case, it has been tested in patients with cardiovascular disease to reduce the risk of myocardial infarct. Its function as an anticoagulant has also been explored in the prophylaxis and treatment of pre-eclampsia, where due to its anti-inflammatory properties, aspirin intake may be used to reduce the risk of colorectal cancer. It is important to always consider both the risks and benefits of aspirin's application. This is especially important for proposed use in the prevention and treatment of neurologic ailments like Alzheimer's disease, or in the prophylaxis of myocardial infarct. In such cases, the decision if aspirin should be applied, and at what dose may be guided by specific molecular markers. In this revived paper, the pleiotropic application of aspirin is summarized.
Topics: Animals; Aspirin; Female; Humans; Mental Disorders; Neoplasms; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy
PubMed: 31669590
DOI: 10.1016/j.ejphar.2019.172762 -
The Canadian Journal of Cardiology May 2022Patients with widespread atherosclerosis such as peripheral artery disease (PAD) have a high risk of cardiovascular and limb symptoms and complications, which affects...
Patients with widespread atherosclerosis such as peripheral artery disease (PAD) have a high risk of cardiovascular and limb symptoms and complications, which affects their quality of life and longevity. Over the past 2 decades there have been substantial advances in diagnostics, pharmacotherapy, and interventions including endovascular and open surgical to aid in the management of PAD patients. To summarize the evidence regarding approaches to diagnosis, risk stratification, medical and intervention treatments for patients with PAD, guided by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework, evidence was synthesized, and assessed for quality, and recommendations provided-categorized as weak or strong for each prespecified research question. Fifty-six recommendations were made, with 27% (15/56) graded as strong recommendations with high-quality evidence, 14% (8/56) were designated as strong recommendations with moderate-quality evidence, and 20% (11/56) were strong recommendations with low quality of evidence. Conversely 39% (22/56) were classified as weak recommendations. For PAD patients, strong recommendations on the basis of high-quality evidence, include smoking cessation interventions, structured exercise programs for claudication, lipid-modifying therapy, antithrombotic therapy with a single antiplatelet agent or dual pathway inhibition with low-dose rivaroxaban and aspirin; treatment of hypertension with an angiotensin converting enzyme or angiotensin receptor blocker; and for those with diabetes, a sodium-glucose cotransporter 2 inhibitor should be considered. Furthermore, autogenous grafts are more effective than prosthetic grafts for surgical bypasses for claudication or chronic limb-threatening ischemia involving the popliteal or distal arteries. Other recommendations indicated that new endovascular techniques and hybrid procedures be considered in patients with favourable anatomy and patient factors, and finally, the evidence for perioperative risk stratification for PAD patients who undergo surgery remains weak.
Topics: Canada; Humans; Intermittent Claudication; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Quality of Life; Risk Factors
PubMed: 35537813
DOI: 10.1016/j.cjca.2022.02.029 -
Neurology Jul 2023Ischemic stroke despite a direct oral anticoagulant (DOAC) is increasingly common and portends a high risk of subsequent ischemic stroke. The efficacy and safety of...
BACKGROUND AND OBJECTIVES
Ischemic stroke despite a direct oral anticoagulant (DOAC) is increasingly common and portends a high risk of subsequent ischemic stroke. The efficacy and safety of antithrombotic regimens after the condition are unclear. We aimed to compare the outcomes of patients with ischemic stroke despite DOACs with and without an alternative antithrombotic regimen and determine the risk factors of recurrent ischemic stroke while on anticoagulation.
METHODS
In a population-based, propensity score-weighted, retrospective cohort study, we compared the clinical outcomes of DOAC-to-warfarin switch, DOAC-to-DOAC switch (DOAC), or addition of antiplatelet agents, with those of unchanged DOAC regimen (DOAC) among patients with nonvalvular atrial fibrillation (NVAF) who developed the first ischemic stroke despite a DOAC from January 1, 2015, to December 31, 2020, in Hong Kong. The primary outcome was recurrent ischemic stroke. Secondary outcomes were intracranial hemorrhage, acute coronary syndrome, and death. We performed competing risk regression analyses to compare the clinical endpoints and determined the predictors of recurrent ischemic stroke in an unweighted multivariable logistic regression model.
RESULTS
During the 6-year study period, among 45,946 patients with AF on a DOAC as stroke prophylaxis, 2,908 patients developed ischemic stroke despite a DOAC. A total of 2,337 patients with NVAF were included in the final analyses. Compared with DOAC, warfarin (aHR 1.96, 95% CI 1.27-3.02, = 0.002) and DOAC (aHR 1.62, 95% CI 1.25-2.11, < 0.001) were associated with an increased risk of recurrent ischemic stroke. In the DOAC group, adjunctive antiplatelet agent was not associated with a reduced risk of recurrent ischemic stroke. Diabetes mellitus, concurrent cytochrome P450/P-glycoprotein (CYP/P-gp) modulators, and large artery atherosclerotic disease (LAD) were predictors of recurrent ischemic stroke.
DISCUSSION
In patients with NVAF with ischemic stroke despite a DOAC, the increased risk of recurrent ischemic stroke with switching to warfarin called for caution against such practice, while the increased ischemic stroke with DOAC-to-DOAC switch demands further studies. Adjunctive antiplatelet agent did not seem to reduce ischemic stroke relapse. Because diabetes mellitus, the use of CYP/P-gp modulators, and LAD were predictors of recurrent ischemic stroke, further investigations should evaluate whether strict glycemic control, DOAC level monitoring, and routine screening for carotid and intracranial atherosclerosis may reduce ischemic stroke recurrence in these patients.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that in patients with NVAF experiencing an ischemic stroke while being treated with a DOAC, continuing treatment with that DOAC is more effective at preventing recurrent ischemic stroke than switching to a different DOAC or to warfarin.
Topics: Humans; Warfarin; Anticoagulants; Stroke; Ischemic Stroke; Fibrinolytic Agents; Retrospective Studies; Atrial Fibrillation; Platelet Aggregation Inhibitors; Administration, Oral
PubMed: 37225430
DOI: 10.1212/WNL.0000000000207422 -
Cardiovascular Intervention and... Jan 2022Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myocardial infarction... (Review)
Review
Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Interventional and Therapeutics (CVIT) society proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018. Updated guidelines for the management of AMI were published by the European Society of Cardiology (ESC) in 2017 and 2020. Major changes in the guidelines for STEMI patients included: (1) radial access and drug-eluting stents (DES) over bare-metal stents (BMS) were recommended as a Class I indication, (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. In 2020, updated guidelines for Non-ST-Elevation Myocardial Infarction (NSTEMI) patients, the followings were changed: (1) an early invasive strategy within 24 h is recommended in patients with NSTEMI as a Class I indication, (2) complete revascularization in NSTEMI patients without cardiogenic shock is considered as Class IIa recommendation, and (3) in patients with atrial fibrillation following a short period of triple antithrombotic therapy, dual antithrombotic therapy (e.g., DOAC and single oral antiplatelet agent preferably clopidogrel) is recommended, with discontinuation of the antiplatelet agent after 6 to 12 months. Furthermore, an aspirin-free strategy after PCI has been investigated in several trials those have started to show the safety and efficacy. The Task Force on Primary PCI of the CVIT group has now proposed the updated expert consensus document for the management of AMI focusing on procedural aspects of primary PCI in 2022 version.
Topics: Consensus; Drug-Eluting Stents; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Treatment Outcome
PubMed: 35018605
DOI: 10.1007/s12928-021-00829-9 -
The New England Journal of Medicine Sep 2019There are limited data from randomized trials evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
There are limited data from randomized trials evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease.
METHODS
In a multicenter, open-label trial conducted in Japan, we randomly assigned 2236 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) more than 1 year earlier or who had angiographically confirmed coronary artery disease not requiring revascularization to receive monotherapy with rivaroxaban (a non-vitamin K antagonist oral anticoagulant) or combination therapy with rivaroxaban plus a single antiplatelet agent. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause; this end point was analyzed for noninferiority with a noninferiority margin of 1.46. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority.
RESULTS
The trial was stopped early because of increased mortality in the combination-therapy group. Rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point, with event rates of 4.14% and 5.75% per patient-year, respectively (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P<0.001 for noninferiority). Rivaroxaban monotherapy was superior to combination therapy for the primary safety end point, with event rates of 1.62% and 2.76% per patient-year, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01 for superiority).
CONCLUSIONS
As antithrombotic therapy, rivaroxaban monotherapy was noninferior to combination therapy for efficacy and superior for safety in patients with atrial fibrillation and stable coronary artery disease. (Funded by the Japan Cardiovascular Research Foundation; AFIRE UMIN Clinical Trials Registry number, UMIN000016612; and ClinicalTrials.gov number, NCT02642419.).
Topics: Aged; Aspirin; Atrial Fibrillation; Coronary Artery Bypass; Coronary Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Humans; Kaplan-Meier Estimate; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Purinergic P2Y Receptor Antagonists; Rivaroxaban
PubMed: 31475793
DOI: 10.1056/NEJMoa1904143 -
The Cochrane Database of Systematic... Oct 2019Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay development of pre-eclampsia.
OBJECTIVES
To assess the effectiveness and safety of antiplatelet agents, such as aspirin and dipyridamole, when given to women at risk of developing pre-eclampsia.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (30 March 2018), and reference lists of retrieved studies. We updated the search in September 2019 and added the results to the awaiting classification section of the review.
SELECTION CRITERIA
All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent were included. Studies only published in abstract format were eligible for inclusion if sufficient information was available. We would have included cluster-randomised trials in the analyses along with individually-randomised trials, if any had been identified in our search strategy. Quasi-random studies were excluded. Participants were pregnant women at risk of developing pre-eclampsia. Interventions were administration of an antiplatelet agent (such as low-dose aspirin or dipyridamole), comparisons were either placebo or no antiplatelet.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trials for inclusion and extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For this update we incorporated individual participant data (IPD) from trials with this available, alongside aggregate data (AD) from trials where it was not, in order to enable reliable subgroup analyses and inclusion of two key new outcomes. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
Seventy-seven trials (40,249 women, and their babies) were included, although three trials (relating to 233 women) did not contribute data to the meta-analysis. Nine of the trials contributing data were large (> 1000 women recruited), accounting for 80% of women recruited. Although the trials took place in a wide range of countries, all of the nine large trials involved only women in high-income and/or upper middle-income countries. IPD were available for 36 trials (34,514 women), including all but one of the large trials. Low-dose aspirin alone was the intervention in all the large trials, and most trials overall. Dose in the large trials was 50 mg (1 trial, 1106 women), 60 mg (5 trials, 22,322 women), 75mg (1 trial, 3697 women) 100 mg (1 trial, 3294 women) and 150 mg (1 trial, 1776 women). Most studies were either low risk of bias or unclear risk of bias; and the large trials were all low risk of bas. Antiplatelet agents versus placebo/no treatment The use of antiplatelet agents reduced the risk of proteinuric pre-eclampsia by 18% (36,716 women, 60 trials, RR 0.82, 95% CI 0.77 to 0.88; high-quality evidence), number needed to treat for one women to benefit (NNTB) 61 (95% CI 45 to 92). There was a small (9%) reduction in the RR for preterm birth <37 weeks (35,212 women, 47 trials; RR 0.91, 95% CI 0.87 to 0.95, high-quality evidence), NNTB 61 (95% CI 42 to 114), and a 14% reduction infetal deaths, neonatal deaths or death before hospital discharge (35,391 babies, 52 trials; RR 0.85, 95% CI 0.76 to 0.95; high-quality evidence), NNTB 197 (95% CI 115 to 681). Antiplatelet agents slightly reduced the risk of small-for-gestational age babies (35,761 babies, 50 trials; RR 0.84, 95% CI 0.76 to 0.92; high-quality evidence), NNTB 146 (95% CI 90 to 386), and pregnancies with serious adverse outcome (a composite outcome including maternal death, baby death, pre-eclampsia, small-for-gestational age, and preterm birth) (RR 0.90, 95% CI 0.85 to 0.96; 17,382 women; 13 trials, high-quality evidence), NNTB 54 (95% CI 34 to 132). Antiplatelet agents probably slightly increase postpartum haemorrhage > 500 mL (23,769 women, 19 trials; RR 1.06, 95% CI 1.00 to 1.12; moderate-quality evidence due to clinical heterogeneity), and they probably marginally increase the risk of placental abruption, although for this outcome the evidence was downgraded due to a wide confidence interval including the possibility of no effect (30,775 women; 29 trials; RR 1.21, 95% CI 0.95 to 1.54; moderate-quality evidence). Data from two large trials which assessed children at aged 18 months (including results from over 5000 children), did not identify clear differences in development between the two groups.
AUTHORS' CONCLUSIONS
Administering low-dose aspirin to pregnant women led to small-to-moderate benefits, including reductions in pre-eclampsia (16 fewer per 1000 women treated), preterm birth (16 fewer per 1000 treated), the baby being born small-for-gestational age (seven fewer per 1000 treated) and fetal or neonatal death (five fewer per 1000 treated). Overall, administering antiplatelet agents to 1000 women led to 20 fewer pregnancies with serious adverse outcomes. The quality of evidence for all these outcomes was high. Aspirin probably slightly increased the risk of postpartum haemorrhage of more than 500 mL, however, the quality of evidence for this outcome was downgraded to moderate, due to concerns of clinical heterogeneity in measurements of blood loss. Antiplatelet agents probably marginally increase placental abruption, but the quality of the evidence was downgraded to moderate due to low event numbers and thus wide 95% CI. Overall, antiplatelet agents improved outcomes, and at these doses appear to be safe. Identifying women who are most likely to respond to low-dose aspirin would improve targeting of treatment. As almost all the women in this review were recruited to the trials after 12 weeks' gestation, it is unclear whether starting treatment before 12 weeks' would have additional benefits without any increase in adverse effects. While there was some indication that higher doses of aspirin would be more effective, further studies would be warranted to examine this.
Topics: Aspirin; Female; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Maternal Mortality; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Premature Birth; Prenatal Care; Randomized Controlled Trials as Topic
PubMed: 31684684
DOI: 10.1002/14651858.CD004659.pub3 -
Seminars in Neurology Jun 2023The aim of this review is to provide an overview of the use of antiplatelet medication in neurointervention, with a focus on the clinical indications for antiplatelet... (Review)
Review
The aim of this review is to provide an overview of the use of antiplatelet medication in neurointervention, with a focus on the clinical indications for antiplatelet use in both preventing and reducing platelet aggregation. This review will cover current antiplatelet medications, pharmacokinetics, and pharmacodynamics. We will provide an overview of different endovascular devices and discuss the antiplatelet regimes in neurointervention, highlighting gaps in evidence and scope for future studies.Two randomized controlled trials have evaluated antiplatelet use in the setting of acute large vessel occlusion stroke, with neither demonstrating benefit in their overall cohorts. Evidence on antiplatelet medication for both acute and elective stenting for acute stroke and treatment of cerebral aneurysms is currently based on large case series, and practice in neurointervention has increasingly utilized dual antiplatelet regimes with clopidogrel and second-line agents like prasugrel and ticagrelor. Clopidogrel function testing has an increasing role in neurointerventional procedures, particularly for high metal surface area stents such as the braided flow diverter type stents. Intravenous glycoprotein IIB/IIIA inhibitors have been utilized for both acute bridging and rescue therapy.Antiplatelet decision making is complex, and there are few randomized control trials to guide clinical practice. Comparative trials to guide decision making remain important in both the acute and elective settings. Standardised protocols incorporating platelet function testing may play a role in assisting decision making until more robust clinical evidence is available, particularly in the context of acute neurointerventional stenting for stroke and ruptured cerebral aneurysms.
Topics: Humans; Platelet Aggregation Inhibitors; Clopidogrel; Intracranial Aneurysm; Ticagrelor; Stroke; Treatment Outcome
PubMed: 37562452
DOI: 10.1055/s-0043-1771383 -
JAMA Cardiology Jun 2023Selecting the optimal antiplatelet agent in patients who have received percutaneous coronary intervention is especially important in those with diabetes due to the... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Selecting the optimal antiplatelet agent in patients who have received percutaneous coronary intervention is especially important in those with diabetes due to the heightened risk of ischemic events in this population. Studies on the efficacy and safety of clopidogrel vs aspirin for long-term maintenance after percutaneous coronary intervention in patients with diabetes are lacking.
OBJECTIVE
To investigate cardiovascular outcomes with clopidogrel vs aspirin in patients with and without diabetes.
DESIGN, SETTING, AND PARTICIPANTS
This was a post hoc analysis of the HOST-EXAM randomized clinical trial, an investigator-initiated, prospective, randomized, open-label, multicenter trial performed at 37 centers in Korea. Patients who received dual antiplatelet therapy without clinical events for 6 to 18 months after percutaneous coronary intervention with drug-eluting stents were enrolled from March 2014 to May 2018 with follow-up at 6, 12, 18, and 24 months. All 5438 patients in the original trial were included in this analysis, which was conducted from June to October 2021.
INTERVENTIONS AND EXPOSURES
Enrolled patients were randomized 1:1 to clopidogrel or aspirin monotherapy. Subgroup analyses were performed by the presence of diabetes.
MAIN OUTCOMES AND MEASURES
The main outcome was primary composite end point of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type 3 or 5) at 24-month follow-up.
RESULTS
Of 5438 patients (mean [SD] age, 63.5 [10.7] years; 1384 [25.5%] female), 1860 (34.2%) had diabetes (925 in the clopidogrel arm and 935 in the aspirin arm), and 5338 (98.2%) completed follow-up. The rate of the primary composite end point was significantly lower in the clopidogrel group compared to the aspirin group in patients with diabetes (6.3% vs 9.2%; hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03; absolute risk difference [ARD], 2.7%; number needed to treat [NNT], 37) and without diabetes (5.3% vs 7.0%; HR, 0.76; 95% CI, 0.58-1.00; P = .046; ARD, 1.6%, NNT, 63; P for interaction = .65). The presence of diabetes was not associated with a difference in benefit observed with clopidogrel monotherapy over aspirin for the thrombotic composite end point (HR, 0.68; 95% CI, 0.45-1.04 for patients with diabetes vs HR, 0.68; 95% CI, 0.49-0.93 for those without; P for interaction = .99) and any bleeding with Bleeding Academic Research Consortium 2, 3, or 5 (HR, 0.65; 95% CI, 0.39-1.09 for patients with diabetes vs HR, 0.74; 95% CI, 0.48-1.13 for those without; P for interaction = .71).
CONCLUSION AND RELEVANCE
In this study, clopidogrel monotherapy was associated with a lower rate of the primary composite end point compared to aspirin monotherapy as long-term maintenance therapy after dual antiplatelet therapy for coronary stenting in both patients with and without diabetes. Clopidogrel might thus be considered rather than aspirin in patients who have undergone coronary stenting and successfully completed dual antiplatelet therapy, regardless of diabetes status.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02044250.
Topics: Humans; Female; Middle Aged; Male; Clopidogrel; Aspirin; Platelet Aggregation Inhibitors; Prospective Studies; Drug Therapy, Combination; Hemorrhage; Diabetes Mellitus
PubMed: 37043192
DOI: 10.1001/jamacardio.2023.0592 -
Anticoagulation management in haemodialysis patients with atrial fibrillation: evidence and opinion.Nephrology, Dialysis, Transplantation :... Oct 2022In the absence of robust evidence to guide clinical decision-making, the optimal approach to prevent stroke and systemic embolism in haemodialysis (HD) patients with...
In the absence of robust evidence to guide clinical decision-making, the optimal approach to prevent stroke and systemic embolism in haemodialysis (HD) patients with atrial fibrillation (AF) remains moot. In this position paper, studies on oral anticoagulation (OAC) in HD patients with AF are highlighted, followed by an evidence-based conclusion, a critical analysis to identify sources of bias and practical opinion-based suggestions on how to manage anticoagulation in this specific population. It remains unclear whether AF is a true risk factor for embolic stroke in HD. The currently employed cut-off values for the CHA2DS2-VASc score do not adequately discriminate dialysis patients deriving a net benefit from those suffering a net harm from OAC. Anticoagulation initiation should probably be more restrictive than currently advocated by official guidelines. Recent evidence reveals that the superior benefit-risk profile of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) observed in the general population and in moderate chronic kidney disease can be extended to the HD population. VKA may be especially harmful in dialysis patients and should therefore be avoided, in particular in patients with a high bleeding risk and labile international normalized ratio. Dose-finding studies of DOACs suggest that rivaroxaban 10 mg daily and apixaban 2.5 mg twice daily are appropriate choices in dialysis patients. Combined treatment with oral anticoagulants and antiplatelet agents should be reserved for strong indications and limited in time. Left atrial appendage occlusion is a potential attractive solution to reduce the risk of stroke without increasing bleeding propensity, but it has not been properly studied in dialysis patients.
Topics: Humans; Atrial Fibrillation; Rivaroxaban; Platelet Aggregation Inhibitors; Administration, Oral; Renal Dialysis; Anticoagulants; Stroke; Hemorrhage; Risk Factors; Vitamin K
PubMed: 33647941
DOI: 10.1093/ndt/gfab060